How to control the size and morphology of apatite nanocrystals in bone

Biomineralized materials are highly organized composites with hierarchical structures, in which the basic building blocks (apatite crystals) are generally in the nanometer size range to ensure optimum physical and biological functions (1). The biological mechanisms of tissue development have attracted a great deal of recent attention in fields ranging from biology and chemistry to materials science and bioengineering (2, 3). It is well known that the organic component of bone acts as an important regulator of lattice orientation, particle size, and size distribution in biomineralization processes, but the molecular recognition details at inorganic crystal interfaces are poorly understood (4). Recently, most investigations have been focused on the effects of macromolecules such as carboxylate-rich proteins on hydroxyapatite nucleation and growth because complex interactions and changes of conformation are involved (5, 6). The role of small organic molecules such as citrate was deemphasized and was assumed to be simply that of adsorption on the crystal growth steps, resulting in inhibition of crystal growth (7, 8). However, there is still much to be learned about the mechanisms of crystal size control in biological systems. New insight about the role of citrate is emerging, as illustrated by a study in PNAS (9), in which strongly bound citrate molecules were identified as playing critical roles in interfering with crystal thickening and stabilizing apatite nanocrystal sizes in bone. The report, by Schmidt-Rohr and colleagues (9), focuses on a quantitative analysis of citrate adsorbed on bone surfaces by the use of advanced multi-NMR spectroscopy and distance measurements. It demonstrates that the citrate, strongly immobilized on the surface of bone, accounts for 5.5 wt% of the organic matter in bone. The density of the citrate coverage is approximately one molecule per (2 nm)2, which implies that approximately one sixth of the available apatite …